Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study
Issued Date
2024-01-01
Resource Type
ISSN
09237534
eISSN
15698041
Scopus ID
2-s2.0-85205671136
Pubmed ID
39289145
Journal Title
Annals of Oncology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Annals of Oncology (2024)
Suggested Citation
Lu S., Ahn M.J., Reungwetwattana T., Özgüroğlu M., Kato T., Yang J.C.H., Huang M., Fujiki F., Inoue T., Quang L.V., Sriuranpong V., Vicente D., Fuentes C., Chaudhry A.A., Poole L., Armenteros Monterroso E., Rukazenkov Y., van der Gronde T., Ramalingam S.S. Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study. Annals of Oncology (2024). doi:10.1016/j.annonc.2024.08.2243 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101586
Title
Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study
Author's Affiliation
Osaka International Cancer Institute
Shanghai Chest Hospital
West China School of Medicine/West China Hospital of Sichuan University
National Taiwan University Hospital
Hanoi Medical University
Samsung Medical Center, Sungkyunkwan university
Kanagawa Cancer Center Research Institute
Faculty of Medicine Ramathibodi Hospital, Mahidol University
İstanbul University-Cerrahpaşa Cerrahpaşa Faculty of Medicine
Universidade de São Paulo
AstraZeneca
Faculty of Medicine, Chulalongkorn University
Emory University School of Medicine
Hospital Universitario Virgen Macarena
Centro Medico Dra. de Salvo
Shanghai Chest Hospital
West China School of Medicine/West China Hospital of Sichuan University
National Taiwan University Hospital
Hanoi Medical University
Samsung Medical Center, Sungkyunkwan university
Kanagawa Cancer Center Research Institute
Faculty of Medicine Ramathibodi Hospital, Mahidol University
İstanbul University-Cerrahpaşa Cerrahpaşa Faculty of Medicine
Universidade de São Paulo
AstraZeneca
Faculty of Medicine, Chulalongkorn University
Emory University School of Medicine
Hospital Universitario Virgen Macarena
Centro Medico Dra. de Salvo
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Distant metastases in non-small-cell lung cancer (NSCLC) are a poor prognostic factor that negatively impact quality of life. The central nervous system (CNS) is a common site of distant progression in epidermal growth factor receptor-mutated (EGFRm) NSCLC. Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor recommended for advanced EGFRm NSCLC and as adjuvant treatment for resected EGFRm NSCLC. In LAURA (NCT03521154), osimertinib demonstrated statistically significant improvement in progression-free survival (PFS) versus placebo in unresectable stage III EGFRm NSCLC without progression during/following chemoradiotherapy (CRT). CNS efficacy and time to death or distant metastases (TTDM) analyses are reported here. Patients and methods: Patients without progression during/following definitive platinum-based CRT were randomised 2 : 1 to receive osimertinib (80 mg daily) or placebo until progression [by blinded independent central review (BICR)] or discontinuation. The primary endpoint was PFS by BICR. CNS PFS by neuroradiologist BICR and TTDM by BICR were secondary endpoints. Results: Overall, 216 patients were randomised (143 osimertinib, 73 placebo). Median CNS PFS by neuroradiologist BICR was not reached [95% confidence interval (CI) not calculable (NC)-NC] with osimertinib versus 14.9 months (95% CI 7.4 months-NC) with placebo; hazard ratio (HR) for CNS PFS: 0.17 (95% CI 0.09-0.32). CNS PFS analysis by investigator assessment was consistent with BICR assessment. The cumulative incidence of CNS progression at 12 months was 9% (95% CI 5% to 14%) with osimertinib and 36% (95% CI 24% to 47%) with placebo. There was clinically meaningful improvement in TTDM with osimertinib versus placebo; HR for TTDM: 0.21 (95% CI 0.11-0.38). The cumulative incidence of distant metastases at 12 months was 11% (95% CI 6% to 17%) with osimertinib and 37% (95% CI 26% to 48%) with placebo. Conclusions: Osimertinib demonstrated clinically meaningful improvements in CNS PFS and TTDM versus placebo, supporting osimertinib post-CRT as the standard of care in unresectable stage III EGFRm NSCLC.